EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes
Diabetes Mellitus, Type 1
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes MellitusType 1 Diabetes Mellitus, rhGAD65, GAD65, GAD-Alum, Diabetes Mellitus, Diabetes mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D, Etanercept
Eligibility Criteria
Inclusion Criteria:
- Informed consent given by patients and parent(s)/legal guardian(s)
- Type 1 diabetes according to the ADA classification, diagnosed within the previous 100 days at the time of screening
- Age 8.00 -17.99 years at time of screening
- Fasting C-peptide at time of screening ≥0.12 nmol/L
- Positive for GADA but < 50 000 Units
- Menarchal females must agree to avoid pregnancy and have a negative urine pregnancy test
- Immunity against Varicella, either through previous infection or vaccination
- Patients must follow the Swedish vaccination programme
- Patients of childbearing potential must agree to using adequate contraception, if sexually active, until 1 year after the last administration of GAD-alum and etanercept. Adequate contraception is as follows:
For females of childbearing potential:
- oral (except low-dose gestagen (lynestrenol and norethisterone), injectable, or implanted hormonal contraceptives (females)
- intrauterine device (females)
- intrauterine system (for example, progestin-releasing coil) (females)
- vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)
For males of childbearing potential:
a. Condom (male)
Exclusion Criteria:
- Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
- Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- Treatment with any oral or injected anti-diabetic medications (especially hypoglycemic agents) other than insulin
- Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
- A history of hypercalcemia
- A history of anaemia or significantly abnormal haematology results at screening
- A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
- Clinically significant history of acute reaction to vaccines or other drugs in the past
- Treatment with any vaccine within 4 months prior to planned first administration of GAD-Alum or planned treatment with vaccine up to 4 months after the last injection with GAD-Alum, including influenza vaccine
- Participation in other clinical trials with a new chemical entity within the previous 3 months
- Inability or unwillingness to comply with the provisions of this protocol
- A history of alcohol or drug abuse
- A significant illness other than diabetes within 2 weeks prior to first dosing
- Known human immunodeficiency virus (HIV)
- Prior or active viral hepatitis B or C infection
- Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the GAD-Alum and etanercept administration, respectively)
- Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last GAD-Alum and etanercept administration, respectively
- Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study.
- Deemed by the investigator not being able to follow instructions and/or follow the study protocol
- Active infection, including chronic and local infection or a history of previous tendency to serious infections, recent or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, or known infection with active EBV or CMV
- Hypersensitivity to the active substance in Enbrel (etanercept) or other ingredients in Enbrel
- Active or inactive (latent) tuberculosis (TBC) at screening
- History of malignancy or significant cardiovascular disease
- Current or history of leukopenia, anemia and/or thrombocytopenia
- Liver disease (clinical or hepatic enzymes >3 times the upper limit of normal (ULN))
- Renal insufficiency (clinical or creatinine >3 times the upper limit of normal (ULN))
- MS, undefined neurologic condition or known SLE, or anti-nuclear or known doublestranded DNA antibody positivity
- Arrhythmia
- Pancreatitis
- Vitamin D serum levels >100 nmol/L at screening
Sites / Locations
- Helsingborg Hospital
- Linköping University Hospital
- Lund University Hospital
- Skåne University Hospital, UMAS
- Sachsska, Södersjukhuset
- Uddevalla Hospital
- Västerås Hospital
- Örebro University Hospital
Arms of the Study
Arm 1
Experimental
A
All patients will from Day 1 receive 2 000 IU vitamin D per os per day during 15 months, and from Days 1-90 receive etanercept (Enbrel) injected subcutaneously 0.8 mg/kg body weight (max 50 mg) once a week, and receive 2 subcutaneous injections of 20 μg Diamyd in a prime-and-boost regimen on Days 30 and 60.